Epithelial zonation along the mouse and human small intestine defines five discrete metabolic domains.
Rachel K ZwickPetr KasparekBrisa PalikuqiSara ViragovaLaura WeichselbaumChristopher S McGinnisKara L McKinleyAsoka RathnayakeDedeepya VakaVinh NguyenCoralie TrentesauxEfren ReyesAlexander R GuptaZev J GartnerRichard M LocksleyJames M GardnerShalev ItzkovitzDario BoffelliOphir D KleinPublished in: Nature cell biology (2024)
A key aspect of nutrient absorption is the exquisite division of labour across the length of the small intestine, with individual nutrients taken up at different proximal:distal positions. For millennia, the small intestine was thought to comprise three segments with indefinite borders: the duodenum, jejunum and ileum. By examining the fine-scale longitudinal transcriptional patterns that span the mouse and human small intestine, we instead identified five domains of nutrient absorption that mount distinct responses to dietary changes, and three regional stem cell populations. Molecular domain identity can be detected with machine learning, which provides a systematic method to computationally identify intestinal domains in mice. We generated a predictive model of transcriptional control of domain identity and validated the roles of Ppar-δ and Cdx1 in patterning lipid metabolism-associated genes. These findings represent a foundational framework for the zonation of absorption across the mammalian small intestine.
Keyphrases
- endothelial cells
- stem cells
- machine learning
- gene expression
- induced pluripotent stem cells
- pluripotent stem cells
- transcription factor
- heavy metals
- air pollution
- genome wide
- type diabetes
- metabolic syndrome
- minimally invasive
- fatty acid
- oxidative stress
- mesenchymal stem cells
- deep learning
- artificial intelligence
- risk assessment
- skeletal muscle
- single molecule